A 3-year-old boy presents with failure to thrive, developmental delay, and progressive hepatosplenomegaly. Vital signs reveal HR 102/min, RR 24/min, temperature 37.2°C. Laboratory studies show markedly elevated plasma cholestanol and cholestane-3β,7α,12α-triol levels, with normal LDL cholesterol. Abdominal ultrasound demonstrates hepatic steatosis without cirrhosis. He denies diarrhea. Genetic testing confirms sterol 27-hydroxylase deficiency. Which pathologic process best explains his clinical presentation?
- A)Defective oxysterol formation preventing initiation of bile acid synthesisGABARITO
- B)Decreased SREBP-2 activation impairing cholesterol synthesis upregulation
- C)Accumulation of phospholipids due to blocked sphingomyelinase activity
- D)Inability to form lipoprotein particles in the endoplasmic reticulum
- E)Impaired LDL receptor recycling leading to cellular cholesterol accumulation
Explicação
Cerebrotendinous xanthomatosis (CTX) results from sterol 27-hydroxylase deficiency, blocking the initial oxidation step of cholesterol catabolism to bile acids. This prevents oxysterol-mediated feedback inhibition and leads to accumulation of cholestanol in ti... Ver explicação completa e trilha adaptativa →